Facile Alkyne Assembly-Enabled\nFunctional Au Nanosheets\nfor Photoacoustic Imaging-Guided Photothermal/Gene Therapy of Orthotopic\nGlioblastoma

Treatment of glioblastoma (GBM) remains challenging due\nto the\npresence of blood–brain barrier (BBB) and tumor heterogeneity.\nHerein, Au nanosheets (AuNSs) functionalized with RGD peptides and\nsmall interfering RNA (siRNA), referred to as AuNSs-RGD-CC-siRNA\n(ARCR), are prepared to achieve multimodal therapy for GBM. The AuNSs\nwith a large modifiable surface area, intriguing photothermal conversion\nefficiency (50.26%), and remarkable photothermal stability (44 cycles\nover 7 h) are created using a well-designed amphiphilic surfactant.\nFurthermore, alkynyl groups are assembled onto the Au surface within\n1 min, enabling strong covalent binding of siRNA to AuNSs and thereby\navoiding the interference from biological thiols. Owing to the lipophilicity\nof the surfactant and the targeting property of RGD, ARCR effectively\npasses through the BBB and accumulates in GBM tumor regions, allowing\nnear-infrared photoacoustic imaging-guided photothermal/gene therapy.\nThis work proposes a facile strategy to construct theranostic Au-based\nmaterials, highlighting the potential of multifunctional nanoagents\nfor GBM therapy.